1. Field of the Invention
The field of this invention relates to testing equipment and more particularly to an apparatus which is usable to determine the transfer of a substance through a membrane into a liquid placed in contact with the opposite side of the membrane.
2. Description of the Related Art
There are three ways to apply a medicine to the body of any animal. The most common way probably is to take the medicine orally. The second most common way is direct injection by using a syringe. The third way, which is becoming more common, is by permutation of the drug through the skin.
It is well known to utilize a cream or ointment to be placed on one""s skin for the treating of a disease of the skin. However, what is becoming more common is the use of a drug in the form of an ointment, cream or patch that is to be placed onto the skin for the purpose of the drug entering the human body for the treatment of a medical condition. Transdermal patches are being commonly used, at the present time, for the administration of nitroglycerine for heart patients as well as the applying of nicotine to individuals for the purpose of assisting individuals in stopping smoking.
The usage by human beings and other animals of any topically applied medication depends on the specific knowledge of the transfer kinetics of the active ingredients of the medication on its ability to penetrate through the skin and be absorbed by the animal""s body. It is necessary to know exactly the amount of active ingredients that will penetrate the animal""s skin within a given amount of time. This information is essential to determine the amount of the dosage of medicine to be applied to the skin patch or the amount of ointment or cream that is to be applied to the animal""s skin.
In the past, it has been common to utilize a vertical diffusion cell which is commonly called a Franz cell, named by it""s inventor. The Franz cell is in the form of a container with the upper half separated from the lower half by a porous membrane comprising a barrier. A donor material is placed against the membrane. A receptor fluid, such as a saline solution, is placed within a receptor chamber of the Franz cell container. At predetermined intervals, aliquots are withdrawn from the receptor fluid. Each aliquot is then tested to determine the amount of active medicine that has been absorbed by the receptor fluid.
Generally, the testing of the receptor fluid occurs over a period of hours or days with each sample aliquot withdrawn at certain time intervals apart. Typically, a typical testing apparatus will utilize a plurality of the Franz cells from which there will be automatically removed aliquots from each Franz cell with the aliquot then being tested to determine the quantity of medicine that has been absorbed by the receptor fluid. The reason that a plurality of Franz cells are used is to provide a plurality of readings for the particular donor substance so then an overall average can be arrived at and make a determination of the transfer characteristics of the active ingredients of the donor substance into the receptor fluid. The donor substance could comprise a solid, semi-solid, cream, gel or liquid. Typical donor substances are creams, topical ointments, lotions, or transdermal patches. The active ingredient in the donor substance could comprise a medicine such as an antibiotic or an ophthalmic preparation, cosmetic, pesticide, paint or any potentially toxic substance that would have a tendency to penetrate an animals skin. The receptor fluid normally comprises a saline solution, water or buffered solution. The aliquots, which are to be removed from the receptor fluid, are defined as an exact sub-volume of the overall volume of the receptor fluid.
Generally useful in the whole field of physical chemistry, Franz cells have become particularly useful in the health care field. Transfer kinetics of active substances through the animal skin are determined in order to determine the level of epidermal exposure to pesticides, chemicals, ointments, cosmetics, paints and other substances.
The membrane that is used in conjunction with the Franz cell could comprise cadaver skin or some form of a synthetic membrane that is specifically constructed to essentially duplicate human skin.
One of the objectives of the present invention is to construct a diffusion cell which provides for the withdrawal of aliquots in a manner that does not permit air to be added into the receptor chamber.
Another objective of the present invention is to construct a diffusion cell which provides for accurate replacement in volume of fresh receptor fluid equal to what was withdrawn in each aliquot.
Another objective of the present invention is to construct a diffusion cell which minimizes the volume of the aliquot that is contained within the sampling port thereby having minimal affect on the subsequent aliquot that is withdrawn.
Another objective of the present invention is to incorporate luer fittings in conjunction with the sampling port and refilling port for the receptor fluid which provides for easy connection and disconnection with a withdrawing conduit and a refilling conduit at the same time achieving a leakage free connection.
Another objective of the present invention is to utilize a quick disconnect clamping apparatus in conjunction with the diffusion cell to insure that the donor housing is tightly secured to the main housing of the diffusion cell.
The basic embodiment of diffusion cell of the present invention utilizes a main housing of a container which has a receptor chamber. The receptor chamber has an open top and a closed bottom. A receptor liquid is to be located within the receptor chamber in a sufficient quantity so as to connect with the open top. A receptor liquid refilling port connects with the receptor chamber with this refilling port being located directly adjacent the closed bottom. A sampling port connects with the receptor chamber intermediate the open top and the closed bottom but nearer the open top. A thin membrane is mounted on the main housing extending across the open top effectively closing such. A donor housing has a donor chamber which connects with the membrane. A media is to be supplied to the donor chamber and in contact with the membrane. A quick release clamping apparatus engages with the donor housing function to tightly press the donor housing onto the membrane and the main housing.
A further embodiment of the present invention comprises the main embodiment where the sampling port includes a capillary tube so as to minimize the volume of receptor fluid that is contained within the sampling port upon withdrawing of an aliquot.
A further embodiment of the present invention is where the main embodiment is modified by the donor housing comprising a disc with a center opening which forms the donor chamber. A cover plate is designed to be located over the disc with a cap to be mounted over the cover plate.
A further embodiment of the present invention is where the just previous embodiment is modified by the cap including a viewing port to facilitate visual observation of the receptor chamber in the area of the open top.
A further embodiment of the present invention is where the basic embodiment is modified by the sampling port and the refilling port both having mounted thereon LUER fittings.
A further embodiment of the present invention is where the clamping apparatus is utilized in conjunction with the diffusion cell comprises a pair of plates that define an internal cavity. The main housing is to be inserted within this cavity. One of the plates is mounted against the cap of the donor housing with the other of the plates being fixed to the main housing. A spring biasing arrangement connects between the plates of the clamp of the clamping apparatus therefore tending to maintain a tight connection by the clamping apparatus between the main housing and the donor housing.